Respiratory Viral Infections Flashcards
Why is there a global potential of new respiratory viral epidemics?
viruses mutate and evolve fast; respiratory viruses spread fast by bird or human flight; widely zoonotic; difficult to contain
How does the incidence of respiratory illnessses per person per year change with age?
declines over the course of a lifetime with a peak in the early 20s
What is the percentage of respiratory infections caused by viruses?
75%
What is the type of genetic info in RSV?
RNA
What protein in the virus determines the viral tropism?
viral coat
What is the suffix of all viral families?
viridae
What is the suffix of a viral genus?
virus
What type of virus has quasispecies?
RNA viruses
Give examples of DNA viruses?
poxviruses; herpesviruses
How are DNA viruses adapted to immune pressures?
mimicry
What is a quasispecies?
mutant viruses that develop as a virus replicates in a host
What is the envelope of virsues derived from?
host membrane- lipid
What is found on the outside of viruses that don’t have an evelope?
symmetrical protein capsid
Why is it difficult to block the replicative processes of viruses?
use the host’s biochemistry
Give an example of an infection which has acute viral infection then clearance?
flu
give an example of an infection which shows acute viral infection/clearance and re-infection?
RSV
Give an exmaple of a virus which shows slow chornic infection?
CMV
What is the general mechanism behind viral causes of oncogenesis?
an immune defense against viruses is apoptosis, thereofre viruses turn off this mechnism to survive, but this also results in cancer
What is viral culture?
growing virus in immortalised cell line
What family do the human rhinoviruses come under?
picornaviruses
What type of virus are the influenza viruses?
orthomyxoviruses
What are coronaviruses typically responsible for?
zoonotic transmission and epidemics
What viruses are paramyxoviruses?
RSV; parainfluenza
How many genes does RSV have?
10
What type of genome does RSV have?
ssRNA
Why is RSV able to reinfect?
stimulates poor immunological memory
What is the function of NS1 and NS2 in RSV?
non-structural proteins which have anti-interferon a and b activity
What is the function of N and P genes in RSV?
nucleoprotein and phosphoprotein- nucleocapsid proteins essential for transcriptional activity
What is the function of M gene in RSV?
matrix protein- viral assembly
What is the function of SH gene in RSV?
small hydrophobic protein- unkown function
What is the function of G gene in RSV?
glycoprotein- viral attachment to the cell
What is the function of F gene in RSV?
fusion protein- viral entry and syncytia formation
What is the function of M2 gene in RSV?
M2:1- transcription elongation factor; M2-2: regulation of viral transcription
What is the function of L gene?
nucleocapsid protein- RNA polymerase
How many strains of RSV are there?
2- A and B
What is RSV associated with in later life of infants it infects?
wheezing/astham (chicken and egg Q– are children more ;ikely to get RSV is predisposed to asthma; or does RSV change lungs)
What is the largest single cause of hsopitalisaiotn in infancy?
RSV
What disease does RSV cause in infants?
bronchiolitis
What age is the highest risk for RSV bronchiolotis?
1-6months
What are the 2 forms of surface glycoproteins on influenza?
neuraminidase (N) and haemagglutinin (H)
What is unique about the genome of influenza viruses compared with otehr respiratory viruses?
have a segmented genome
What is antigenic drift?
minor changes caused by point mutations- slow process – antibody no longer recognises
What is antigenic shift?
multiple alterations in antigenic makeup due to reassortment of genome segments; rapid process associated with pandemic outbreaks
Describe the pathogenicitiy of H5N1?
can replicate efficiently only in cells in the lower region of resp tract where the avianvirus receptor is prevalent- if gets into lower airways causes havoc but limited in its chances of getting there- mainly poultry workers
Where were >70s not affected by H1N1?
similar virus in the 1960s so immunological memory
Why is influenza difficult to prevent the transmission of?
very infecitous when asymptomatic
How amny serotypes are there of human rhinoviruses?
> 100
What is the second main cause of hospitalisation in children under 5 years?
parainfluenza
What disease is parainfluenza assocaited with ?
croup
What is the evidence that RSV disease isn’t caused by virus directly but immunopathology?
illness is after the peak viral load, SCID mice do not get normal RSV pathology, instead are overwhelmed by virus after WT mice have cleared infection
What form does prophylaxis of viral infection take?
passive transfer of antibody to block disease
When are antivirals particularly effective?
when viral pathogenesis/persistence is the problem
Why would anti-RSV drug not work in acute infection?
by the time giving antivirals in response to symptosm , too late as viral peak has already happened, symptoms happeneing as result
What is hte problem with tinkering with inflammation e.g anti-TNF?
very dependent upon timing as during peak viral load need to boost inflam whereas need to dampen inflammation during actual disease after viral peak
What is the most common lab abnormality detected in viral infection?
hypoxamia
What are the absolute indications for hospital referrals for acute bronchiolotis?
cyanosis or severe respiratory distress (RR>70; nasa flaring; grunting; chest wall recession); marked lethargy-poor feeding; respiratory distress preventing feeding (<50% usual intake in past 24 hours); apnoeic epsidoes; diagnostic uncertainty
What pulse ox says a baby should be admitted?
<=92
What is the first choice in control of viruses?
vaccination
What is the treatment for bronchiolitis?
supportive- oxygen (intubation; CPAP; head box)’; fluids; +/- antibiotics; vasodilators and CS
How many respiratory infections do children get per year on avergae?
5-6
How many infants with respiratory viral infections will develop lower respiratory tract symptoms ?
1/3rd
give examples of extrapulmonary manifestations of RSV infection?
seizures; hyponatraemia; cardiac arrhythmias; cardiac failure and hepatitis
Which infants are at risk of severe LRTI?
premature and infants with congenital heart disease
Give examples of neuraminidase inhibitors?
oseltamivir and zanamivir
What is the benefit of neuraminidase inhibitors?
shortens symptoms by about 1 day and may reduce disease severity
When are neuraminidase inhibitors helpful?
wihtin 48h of exposure or 36h after first symptoms- not in established influenza infection or sever LRTI
Who should get neuraminidase inhibitors?
for children with chronic morbidity who are at an increased risk of sever influenza-induced disease
What is ribavirin licensed for?
inhalation for severe RSV bronchiolitis
What is a problem with ribavirin?
teratogenic
Why has ribavirin provided little or no benefit?
once developed, the severe inflammation in RSV bronchioloitis may be maintained independetly of the presence of live RSV virions
Which respiratory infections are cosrticosteroids helpful in?
croup
What are the 4 main ways in which respiratory viruses are diagnosed?
virus culture; serology; immunofluorescen/antigen detection and nucleic acid/PCR based test
What is serology?
blood is tested for either virus-specific antibodies or viral antigen by a functional assay
What is the disadantage of both viral culture and serology?
cultures can take upto 10 days and the antibody response to viral infection can take 2 weeks (infection is often resolved before the infecitous agent is defined)– more useful in epidemiological studies
Whati s the basis of antigen detection?
use of virus-specfic monoclonal antibodies
Which viruses cause bronchiolotis?
influenza; adenovirus; human metapenumovirus; parainfluenza; rhinovirus and RSV
What is the role of viral coinfection in bronchiolitis?
common-20% of cases; depends on whcih viruses coinfect together- increase in severesity with hMPV and RSV but not with RSV+ adenovirus/rhinovirus
What is the benefit of knowledge of the infecting agent?
doesnt alter treatment but will reduce inappropriate antiboitic use and may allow cohorting of patients to reduce nosocomial infection
What are the factors involvedi n likelihood of a respiratory tract infection?
age and exposure to infection
What are the risk factors for severe RSV infection?
age when infected; increased exposure to an infectious agent; decreased body size; protection against virus due to breastfeeding and amount of IgG in breast milke; factors affecting lung function eg smoke and air pollution
What are the factors related to increased exposure to an infectious agen?
siblin order; daycare attendance; birth season; hospitalisation and socioeconomic status
Why does young age act as a metafactor?
age has an effect on the size of hte child- esp airway size; transmission dynamics; immune experience ; have smaller energy reserves and more likely to get exhausted by effort of breathing
What is the ultimate cause of mortality in acute bronchiolitis?
exhuastion due to effort of breathing
Polymrophisms in which genes of the innate immune system result in higher RSV susceptbility?
transcriptional regulator Jun; IFNa; nitric oxide synthase and the vitamin D receptor
What are the 2 groups of genes important for changing the outcome following respiratory viral infection?
first group- involved in the magnitude and type of immune response e.g IL-4 or IL13; second- genes involved in control of viral load e.g TLR4; IL6; CD14
Which TLRs detect viruses extracellularly?
TLR2,6 and 4 (mice deficient in TLR2/6 have increased RSV virla load)
How does RSV interact with TLR4?
via its F protein
What is the function of hte influenza virus NS1 protein?
concelas the viral genome from deetection
How does RSV prevent RIG-I detection?
binds La antigen
What is the effect of RSV on downstream signalling from PRRs?
inhibits IFN production; IRF3 activation is inhibited; although NF-kB increases following RSV (prevent apoptosis); IFNa receptor signalling by the JAK-STAT pathway
How is the adaptive immune repsonse evaded by respiratory viruses priamrily?
mutation of viral proteins
Which is the main respiratory virus that does not have an RNA genome?
adenovirus
What effect does increasing glyosylation of the coat proteins of a virus have?
increased immune evasion
What does influenza use to inhibit DC function?
haemagglutinin and NS1 proteins
What suggests that lung damage caused by the virus is a key factor in pathology?
correlation bewteen viral load and disease severity; RSV cause inhibit cilia movement leading to airway blockade; study of infants who died of RSV showed presence of virus but not lymphocytes- however this might be due to immunodeficiency; RV causes cytotoxicity in vitro; inhibiting cytokein response had not effect on H5N1 pathogeneisis; IL-1 deficiency mice had worse pathology with influenza
What evidence suggests that immunopathology is responsible for lung damage with respiratory infectiosn?
RSV-child who ided in crash had lots of lymphocytosis; RSV-infected HIV pos infants had icnreased viral shedding but decreased bronchiolitis; data shows patietns who died of SARS or H5N1 had cleared the virus; antiviral drugs did not alter disease outcome; RSV and RV are characterised by neutrophil infiltrate; IL-8 is upregulated in RSV bronchiolitis and asthmatics with RV
What is the function of IL-8
main neutrophil chemosttractant
What are the 2 main methods by which viral infection enhances bacterial infections?
altering physical barriers and altering immune system barriers
How does the viral infection alter the physical barriers ?
may damage lung epithelia (virus and immune response); neuraminidase thins mucus and exposes receptors onf epithelial cells- increased bacterial infectivity
How does influenza alter the immune response?
inhibit neutrophilia
When does bacterial coinfection tend to happen with viral infections?
later stages of viral infection- during dampening of immune repsonse e.g IL10 upregulation can lead to increased bacterial infection; general downregulation of pathogen sensing following viral infection
Why do infants have a tendency towards hyporesponsive immune responses?
critical to survive exposure to previously unseen nonpathogenic antigens of both self and foregin origins
what type of Th response are infant immune responses skewed towards and why?
Th2- reflection of pregnancy- to avoid rejection, Th1 in pregnnacy is associated with preeclampsia, infections eg chlamydia which stimualte Th1 assoc. with abortion
Which respiratory viruses have an associated with later-life wheezing?
hMPV; RV and RSV
What virus is ribavirin used for?
RSV
What is the problem with antivirals in general?
very prone to inducing viral escape mutatns eg oseltamivir resistnace only requires a single point mutation
Give an example of passive immunisation?
palivizumab- monoclonal antibody against RSV
If infants have immune hyporesponsiveness, how is there a problem with immunopathology?
have reduced IFN and th1 responses; with increased IL23 and Th17; reduced immunoregulation(IFN increases IDO); lack of previous exposure to virus- increased viral load–resulting response is greater
What should be considered with the possiblity of vaccinating against viral infections early in life?
infection is important in the development of normal immune responses thereofre vaccination coverage may have an impact on immunity development and more severe infection/asthma later in life
